Background/Aim: To determine the yield of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in combination with immunostains in diagnosing unusual solid pancreatic masses (USPM) in comparison with pancreatic adenocarcinoma (ACP). Patients and Methods: All EUS-FNA of solid pancreatic masses performed with a 22-gauge needle were included. Data on clinical presentations, mass characteristics, presence of pancreatitis, yield of tissue, and final diagnosis were compared between the two groups. On site cytopathology was provided and additional passes were requested to perform immunostains. Results : Two hundred and twenty-nine cases with either adenocarcinoma or USPM were included. The median age of the cohort was 65 years. ACP (210/229, 92%) accounted for the majority of the cases. The USPM included neuroendocrine (NET) masses (n=13), metastatic renal carcinoma (n=3), metastatic melanoma (n=1), lymphoma (n=1), and malignant fibrous histiocytoma (n=1). Subjects with ACP were significantly more likely to present with loss of weight (P=0.02) or obstructive jaundice (P<0.001). Subjects with ACP were more likely to have suspicious/atypical FNA biopsy results as compared with USPM (10% vs 0%). The sensitivity of EUS-FNA with immunostains was 93% in ACP as compared with 100% in USPM. Diagnostic accuracy was higher in USPM as compared with ACP (100% vs 93%). Conclusions: EUS-FNA using a 22-gauge needle with immunostains has excellent diagnostic yield in patients with USPMs, which is comparable if not superior to the yield in pancreatic adenocarcinoma.